title: Yap1 acts downstream of α-catenin to control epidermal proliferation.
abstract: During development and regeneration, proliferation of tissue-specific stem cells is tightly controlled to produce organs of a predetermined size. The molecular determinants of this process remain poorly understood. Here, we investigate the function of Yap1, the transcriptional effector of the Hippo signaling pathway, in skin biology. Using gain- and loss-of-function studies, we show that Yap1 is a critical modulator of epidermal stem cell proliferation and tissue expansion. Yap1 mediates this effect through interaction with TEAD transcription factors. Additionally, our studies reveal that α-catenin, a molecule previously implicated in tumor suppression and cell density sensing in the skin, is an upstream negative regulator of Yap1. α-catenin controls Yap1 activity and phosphorylation by modulating its interaction with 14-3-3 and the PP2A phosphatase. Together, these data identify Yap1 as a determinant of the proliferative capacity of epidermal stem cells and as an important effector of a "crowd control" molecular circuitry in mammalian skin.
authors.affiliation: Stem Cell Program, Children's Hospital, Boston, MA 02115, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Schlegelmilch
authors.forename: Morvarid
authors.initials: M
authors.lastname: Mohseni
authors.forename: Oktay
authors.initials: O
authors.lastname: Kirak
authors.forename: Jan
authors.initials: J
authors.lastname: Pruszak
authors.forename: J Renato
authors.initials: JR
authors.lastname: Rodriguez
authors.forename: Dawang
authors.initials: D
authors.lastname: Zhou
authors.forename: Bridget T
authors.initials: BT
authors.lastname: Kreger
authors.forename: Valera
authors.initials: V
authors.lastname: Vasioukhin
authors.forename: Joseph
authors.initials: J
authors.lastname: Avruch
authors.forename: Thijn R
authors.initials: TR
authors.lastname: Brummelkamp
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Camargo
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D049109:Cell Proliferation; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D000091102:YAP-Signaling Proteins; D051178:alpha Catenin / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D051178:alpha Catenin